CN107362164A - 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用 - Google Patents

吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用 Download PDF

Info

Publication number
CN107362164A
CN107362164A CN201710783653.5A CN201710783653A CN107362164A CN 107362164 A CN107362164 A CN 107362164A CN 201710783653 A CN201710783653 A CN 201710783653A CN 107362164 A CN107362164 A CN 107362164A
Authority
CN
China
Prior art keywords
pirfenidone
medicine
lupus nephritis
application
kidney fibrosis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710783653.5A
Other languages
English (en)
Inventor
达展云
何亚运
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affiliated Hospital of Nantong University
Original Assignee
Affiliated Hospital of Nantong University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Affiliated Hospital of Nantong University filed Critical Affiliated Hospital of Nantong University
Priority to CN201710783653.5A priority Critical patent/CN107362164A/zh
Publication of CN107362164A publication Critical patent/CN107362164A/zh
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了一种吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用。本发明提供了一种吡非尼酮的新用途，吡非尼酮是一种新的安全、有效治疗狼疮肾炎肾纤维化的药物。

Description

吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用
技术领域
本发明涉及一种吡非尼酮的用途。
背景技术
系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种可累及多系统的自身免疫性疾病，以体液免疫为主，其主要发病机制与相关抗体、补体形成免疫复合物和炎症细胞作用于微血管引起组织损伤有关，而肾脏毛细血管袢丰富，因此肾脏是其主要受累器官之一。狼疮肾炎（lupus nephritis, LN）是系统性红斑狼疮（SLE）发生率最高的并发症，其确切的免疫发病机制尚未完全明了。关于狼疮肾炎的治疗，尽管近年来有了一定进展，包括糖皮质激素、免疫抑制剂、生物制剂等药物的干预，若不及时、有效的控制其发展，仍有10%-30%的狼疮肾炎患者在发病后5-10年进展至终末期肾衰竭。SLE晚期发生肾纤维化，预后很差。因此积极、早期干预对于系统性红斑狼疮肾炎的治疗尤为关键。临床上目前尚无明确、有效的治疗肾纤维化的药物。
吡非尼酮（pirfenidone, PFD）是一种分子式为C12H11NO、相对分子质量185.22的具有广谱抗纤维化作用的新型药物，其化学名称为 5-甲基-1-苯基-2-吡啶酮。国外大量的研究已经证实吡非尼酮是一种有效的细胞因子抑制剂，可以调节许多致纤维化细胞因子，包括转化生长因子-β（TGF-β）、结缔组织生长因子（CTGF）、肿瘤坏死因子（TNF-α）和血小板衍生因子（PDGF），抑制成纤维细胞的生物学活性，改变胶原表达的合成和累积，抑制细胞外基质的增殖和表达，具有强大的抗炎、抗氧化以及抗纤维化的作用。在日本、欧美等国家，吡非尼酮已经通过期临床试验阶段，正式用于特发性肺纤维化（idiopathic pulmonaryfibrosis, IPF）的治疗。
发明内容
本发明的目的在于提供一种的新用途，是吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用。
本发明的技术解决方案是：
一种吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用。
本发明提供了一种吡非尼酮的新用途，吡非尼酮是一种新的安全、有效治疗狼疮肾炎肾纤维化的药物。
下面结合实施例对本发明作进一步说明。
具体实施方式
一种吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用。
动物实验：
一、方法
1. 实验分组：Balb/c雌性小鼠8只，设为健康对照组。40只MRL/lpr雌性小鼠随机分为未治疗组（n=8）、羧甲基纤维素钠对照组（n=4）、强的松治疗组(n=14)、强的松+吡非尼酮治疗组(n=14)。未治疗组和健康对照组无任何处理，其余各组狼疮小鼠20周龄时进行每日灌胃治疗。羧甲基纤维素钠对照组予同治疗组等体积的羧甲基纤维素钠，强的松治疗组予强的松，强的松+吡非尼酮治疗组予强的松+吡非尼酮，干预12周。
2.观察指标及检测方法：（1）小鼠的一般情况（毛发、活动度、摄食、体重变化）。（2）收集24小时尿液、小鼠血清标本检测24小时尿蛋白定量、免疫荧光法检测抗ANA抗体滴度、全自动生化分析仪测定谷丙转氨酶（ALT）、谷草转氨酶（AST）、肌酐（Scr）、胱抑素C（CysC）、β2微球蛋白（β2-MG）。（3）酶联免疫吸附法检测血清抗ds-DNA抗体水平。（4）肾脏HE、Masson、PASM染色，光学显微镜下观察肾组织的病理改变。（5）Western Blot检测肾组织中TGF-β1、CTGF的表达情况。（6）免疫组化法检测肾组织中α-SMA的表达情况。
二、结果
1. 吡非尼酮+强的松组治疗组小鼠一般情况良好，体重与同龄的未治疗组比较上升。
2. 吡非尼酮+强的松组治疗组小鼠24h尿蛋白定量下降。
3. 吡非尼酮+强的松组抗ds-DNA抗体水平下降。
4. 吡非尼酮+强的松组抗ANA抗体滴度下降。
5. 吡非尼酮+强的松组抗ANA抗体滴度下降肾功能改善，血清肌酐水平和胱抑素C水平均下降。
6.强的松组和吡非尼酮+强的松组的肾脏病理损害均较未治疗组减轻，其中吡非尼酮+强的松组肾脏病理损害轻于强的松组。
7.吡非尼酮+强的松治疗组肾脏纤维化指标，如TGF-β1、CTGF、α-SMA的表达较强的松组下降，差异有统计学意义。
三、结论
吡非尼酮能降低MRL/lpr狼疮小鼠的蛋白尿，降低抗ds-DNA抗体和抗ANA抗体的滴度，改善肾功能，减少肾组织的病理损害，通过抑制TGF-β1、CTGF、α-SMA的表达，减轻肾脏纤维化，延缓病情发展。吡非尼酮对治疗狼疮小鼠肾炎慢性进程所致的肾脏纤维化有一定疗效。治疗剂量的吡非尼酮无明显肾毒性。

Claims (1)

1.一种吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用。
CN201710783653.5A 2017-09-04 2017-09-04 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用 Pending CN107362164A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710783653.5A CN107362164A (zh) 2017-09-04 2017-09-04 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710783653.5A CN107362164A (zh) 2017-09-04 2017-09-04 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用

Publications (1)

Publication Number Publication Date
CN107362164A true CN107362164A (zh) 2017-11-21

Family

ID=60312154

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710783653.5A Pending CN107362164A (zh) 2017-09-04 2017-09-04 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用

Country Status (1)

Country Link
CN (1) CN107362164A (zh)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060110358A1 (en) * 2002-08-28 2006-05-25 Hsu Henry H Combination therapy for treatment of fibrotic disorders

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060110358A1 (en) * 2002-08-28 2006-05-25 Hsu Henry H Combination therapy for treatment of fibrotic disorders

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MOHAMMED ALI AL-BAYATI, ET.AL: "Effect of pirfenidone against vanadate-induced kidney fibrosis in rats", 《BIOCHEMICAL PHARMACOLOGY》 *

Similar Documents

Publication Publication Date Title
Wu et al. Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune response in rheumatoid arthritis
Reardon et al. Obesity and insulin resistance promote atherosclerosis through an IFNγ-regulated macrophage protein network
Wu et al. Probiotics (Lactobacillus plantarum HNU082) supplementation relieves ulcerative colitis by affecting intestinal barrier functions, immunity-related gene expression, gut microbiota, and metabolic pathways in mice
Tan et al. Inhibition of BRD4 suppresses tumor growth in prostate cancer via the enhancement of FOXO1 expression
Ahn et al. Renoprotective effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, on rats with chronic kidney disease
Zhu et al. Protective effects of Huang Qi Huai granules on adriamycin nephrosis in rats
Cao et al. Orally administration of cerium oxide nanozyme for computed tomography imaging and anti-inflammatory/anti-fibrotic therapy of inflammatory bowel disease
Wu et al. Store–operated Ca2+ channels in mesangial cells inhibit matrix protein expression
Xiao et al. Qing-dai powder promotes recovery of colitis by inhibiting inflammatory responses of colonic macrophages in dextran sulfate sodium-treated mice
JP6905140B2 (ja) 炎症性腸疾患の治療におけるアルテミシニン誘導体の医学的使用
Qin et al. Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-β1/p38MAPK/Smad2/3 pathway
Hong et al. D-ribose induces nephropathy through RAGE-dependent NF-κB inflammation
Liu et al. Exercise induced meteorin-like protects chondrocytes against inflammation and pyroptosis in osteoarthritis by inhibiting PI3K/Akt/NF-κB and NLRP3/caspase-1/GSDMD signaling
Huang et al. Effect of qufengtongluo decoction on PI3K/Akt signaling pathway in the kidney of type 2 diabetes mellitus rat (GK rat) with diabetic nephropathy
Sun et al. Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling
Zhou et al. Sodium butyrate attenuates diabetic kidney disease partially via histone butyrylation modification
Yang et al. Hirudin Ameliorates Renal Interstitial Fibrosis via Regulating TGF‐β1/Smad and NF‐κB Signaling in UUO Rat Model
Wang et al. Butylphthalide ameliorates airway inflammation and mucus hypersecretion via NF-κB in a murine asthma model
Zhao et al. Improvement of Non‐Alcoholic Fatty Liver Disease in Mice by Intermittent Use of a Fasting‐Mimicking Diet
CN107362164A (zh) 吡非尼酮在制备治疗狼疮肾炎肾纤维化的药物中的应用
Kim et al. A new murine liver fibrosis model induced by polyhexamethylene guanidine-phosphate
Wang et al. The protective effects of cobra venom from Naja naja atra on acute and chronic nephropathy
Lv et al. A traditional clinic Chinese medicine prescription Qu‐Zhuo‐Tong‐bi (QZTB) alleviates gouty arthritis in model rats
CN102716123A (zh) 一种用于治疗IgA肾病复方制剂
Li et al. Blocking posttranslational core fucosylation ameliorates rat peritoneal mesothelial cell epithelial-mesenchymal transition

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20171121

RJ01 Rejection of invention patent application after publication